Alveolar macrophages play a paramount role in maintaining lung homeostasis. Environmental agents, implicated in the etiology of chronic obstructive lung disease have been shown to alter macrophage behavior, and it is hypothesized that these alterations are critical to the development of disease. We suggest that the pinocytic activity of alveolar macrophages is responsible for removal from the alveoli of hydrolytic enzymes. The ability of macrophages to remove potentially injurious agents is enhanced by the presence of high affinity surface receptors. In previous studies we defined the interaction between alpha 2 macroglobulin protease complexes and macrophage surface receptors, and demonstrated the receptors were recycled. In this application we plan to determine the mechanism(s) of receptor mediated endocytosis and membrane recycling. To define macrophage membrane components involved in endocytosis, approaches are outlined to identify and isolate surface receptors for alpha macroglobulin-protease complexes. Among the approaches are ligand-directed iodination, using lactoperoxidase that has been chemically coupled to alpha macroglobulin trypsin complexes, and the use of a novel series of heterofunctional photoaffinity probes. Alpha M T-receptor complexes will be used as an immunogen to obtain monoclonal antireceptor antibodies. With such antibodies, (or with the ability to identify receptor molecules), we can determine whether receptors are internalized and define mechanisms of membrane turnover. We also propose to examine the hypothesis that surface receptors for fucose terminal glycoprotein, such as lactoferrin, are not reutilized. We propose to determine the topographical distribution of macrophage receptors (for alpha macroglobulin-protease complexes, mannose-terminal or fucose-terminal glycoprotein) using both biochemical (ligand directed iodination) morphological techniques (ferritin or hemocyanin coupled to anti-receptor antibody or ligand in conjunction with electron microscopy). These approaches will be used to determine the native as well as ligand or drug (chloroquine, methyl amine)-induced, distribution of surface receptors. These approaches will allow us to map the distribution of macrophages membrane components as well as to determine the factors that specify receptor mediated endocytosis and recycling.